https://scholars.lib.ntu.edu.tw/handle/123456789/188198
標題: | 肺癌醣化酵素基因異常調控之研究(1/3) | 其他標題: | Dysregulation of Glycosyltransferase Genes in Lung Cancer | 作者: | 余忠仁 | 關鍵字: | 肺癌;醣化酵素基因;Lung cancer;glycosyltransferase | 公開日期: | 2003 | 出版社: | 臺北市:國立臺灣大學醫學院內科 | 摘要: | 黏液素被認為與癌細胞之局部侵犯與遠隔轉移有關,由於癌細胞之黏液素基 因表現及其醣化過程異於正常細胞,有利其脫離局部病灶,並逃避宿主之免疫系 統攻擊。在吾人先前之研究中,已證實肺癌會發生黏液素基因之變異,而此變異 與異常醣化過程(涎黏液素之產生)均與肺癌病患術後之預後有關。同時並發現 涎黏液素之發生與致癌基因neu/ erbB-2 有明顯相關性。吾人先前利用multiplex PCR 探討肺癌之醣化酵素基因表現(包括sialyltransferase ,STs ;與 fucosyltransferase ,FucTs ),侵犯力高易轉移的細胞株(CL1-5 )其STs 與FucTs 之表現量高於侵犯力弱的母細胞株(CL1-0 、CL1-1 )。臨床上,超過50%肺癌檢體 有STs 與FucTs 表現量增加之現象,而表現高量ST3GalIII 與數種FucTs (FucTIII 、IV 、VI 、VII )之肺癌患者其臨床預後明顯較差,術後復發高與長期 存活率低。本三年研究計劃之目的為:(1)廣泛而完整的探討醣化酵素基因 (core1-4GnTs 、b-1-4GalT I~VI 、GlcNAcT I-VI )在肺癌之表現情形以及與肺癌 預後及臨床表現之相關聯性;(2)對於由(1)所選出具臨床重要性之醣化酵素基 因,探討基因表現之調控機轉。於第一年研究中,我們探討N-acetylglucosaminyl-transferase (MGAT) I~V 在肺癌之表現量與臨床特徵及預後之相關性。 Mucins and mucin associated antigens are believed to play an important role in both invasion and metastasis of cancer cells. The altered expression of mucin peptides in cancer cells, as well as glycosylation, facilitates tumor cell invasion into blood stream, attachment to endothelial cells and escape from host immuno-surveillance. Our previous studies had demonstrated the prognostic implication of mucin expression for lung cancer. Lung cancers overexpressing sialomucins tend to have higher chance of recurrence and metastasis. The expression of sialomucin is correlated with the overexpression of an oncoprotein, erbB-2/neu, and at least one mucin gene ( MUC5AC apomucin). We are than interested about the altered expression of glycosyltransferase genes in lung cancer. Preliminarily, using multiplex PCR to evaluate the expression of sialyltransferase(ST) and fucosyltransferase (FucT) gene families in lung cancer (in >50% of patients), we have demonstrated that overexpression of STs and FucTs are common in lung cancer tissues and cell lines. Daughter cell line (CL1-5) with high invasiveness and metastasis ability expressed more STs and FucTs than parent cell line (CL1-0 and CL1-1). Clinically, patients bearing tumors with overexpression of ST3GalIII and FucTIII 、IV 、VI 、VII are liable to cancer recurrence and death. We thus propose a three-year study to comprehensively study the role of glycosyltransferase genes expression in lung cancer. Is up-regulation or down-regulation of certain glycosyl -transferase which leads to expression of cancer-associated sialylated antigens occurs preferentially in lung cancer? Can the altered expression of glycosyltransferase genes serve as a prognostic marker? Specific glycosyltransferase genes considered to be important in lung cancers will be cloned and subjected to further study. In the first year, we evaluated the expression of N-acetyl -glucosaminyltransferase (MGAT) I~V in lung cancer and the association of MGAT expression with clinical features and prognosis of lung cancer. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/23597 | 其他識別: | 912314B002268 | Rights: | 國立臺灣大學醫學院內科 |
顯示於: | 醫學系 |
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912314B002268.pdf | 268.17 kB | Adobe PDF | 檢視/開啟 |
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